Lamin depolymerization

Abstract: The cytoplasmic and nuclear compartments of animal cells mix during mitosis on disassembly of the nuclear envelope (NE). NE breakdown (NEBD) involves the dispersion of the nuclear membranes and associated proteins, including nuclear pore complexes (NPCs) and the nuclear lamina. Among the approximately 30 NPC components known, few contain transmembrane domains. gp210 is a single-pass transmembrane glycoprotein of metazoan NPCs. We show that both RNAi-mediated depletion and mutation of Caenorhabditis elegans gp210 affect NEBD in early embryonic cells, preventing lamin depolymerization and leading to the formation of twinned nuclei after mitosis owing to physical interference with normal chromosome alignment and segregation. When added to in vitro assembled nuclei, antibodies specific for the C-terminal cytoplasmic tail of gp210 completely blocked NEBD. This treatment inhibited mitotic hyper-phosphorylation of gp210. Phosphorylation of gp210 is proposed to be mediated by cyclin-B-cdc2 and we show that depletion of cyclin B from C. elegans embryos also leads to a nuclear-twinning phenotype. In summary, we show that gp210 is important for efficient NPC disassembly and NEBD and suggest that phosphorylation of gp210 is an early event in NEBD that is required for lamin disassembly and other aspects of NEBD.